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A submaximal all-extremity exercise test to predict maximal oxygen consumption.

PURPOSE: Submaximal aerobic exercise testing is utilized with a variety of populations to assess fitness level and predict maximal oxygen uptake (VO2peak) when a maximal test is not possible or preferable. Many submaximal tests have been developed on traditional exercise equipment, such as the treadmill and the cycle ergometer, but are not available for newer equipment such as an all-extremity ergometer. The purpose of this study was to develop and validate a submaximal exercise test using the Pro II Power Trainer, an all-extremity ergometer, in women ages 30-60 without disability and with varying fitness levels. A secondary purpose was to compare VO2peak values achieved during the all-extremity maximal test and the treadmill test. METHODS AND RESULTS: A linear regression equation was developed to predict VO2peak from submaximal data using heart rates and power output at the sixth and ninth minutes of the submaximal test. The linear regression derived for the submaximal all-extremity test was VO2peak L.min-1 = -0.01 (age in years) - 0.0029 (HR 1) - 0.0099 (HR2) - 0.0029 (PO1) + 0.0151(PO2) + 3.010. Predicted residual sum of squares of the linear equation revealed an R2 value of 0.722 and standard error of estimate of 0.216 L.min-1. Treadmill VO2 speak values correlated strongly with all-extremity VO2 speak values (r = 0.918) and were not significantly different (P, 0.05). CONCLUSION: A similar submaximal test needs to be developed for field estimates of VO2peak for subpopulations of individuals with physical disabilities such as rheumatoid arthritis, head or spinal cord injury, cerebral vascular accident, multiple sclerosis, amputation, and cerebral palsy.

Adult↗

The ATP assay is more sensitive than the succinate dehydrogenase inhibition test for predicting cell viability.

The succinate dehydrogenase inhibition (SDI) test and the adenosine triphosphate (ATP) assay, are both used for in vitro human tumor chemosensitivity testing. We exposed HeLa cells to various concentrations of mitomycin C for 1, 2 or 3 days and found that the decrease in number of viable cells correlated with that of succinate dehydrogenase (EC 1.3.99.1) activity and that of intracellular ATP level of the viable cells. In the dead cells, the ATP level was extensively decreased, but the succinate dehydrogenase activity remained at a level of 24% of that of mitomycin C-untreated viable cells, even on day 3. Thus, the ATP level better reflected the cell viability. In clinical situations, the succinate dehydrogenase activity and the ATP level are assayed in whole cells following exposure to anticancer drugs, therefore the activity remaining in the dead cells must be taken into consideration for the chemosensitive prediction with the SDI test, but not with the ATP assay. This higher sensitivity of the ATP assay will enable a more accurate prediction of cell viability.

Adenosine Triphosphate↗

Protein-energy malnutrition and liver dysfunction limit the usefulness of the relative dose response (RDR) test for predicting vitamin A deficiency.

The relative dose response (RDR) test was examined for its value in predicting vitamin A nutriture among chronically ill patients with protein-energy malnutrition and among patients with varying degrees of liver dysfunction. The RDR test was elevated (ie greater than 14 per cent) and, thus, predictive of vitamin A deficiency in only 4 out of 9 patients with combined vitamin A deficiency and protein-energy malnutrition. Among 27 patients with liver dysfunction who had vitamin A determinations performed on liver biopsy material, there was no correlation found between the RDR response and the hepatic vitamin A level. Of 12 patients with low hepatic vitamin A levels (less than 100 micrograms/g wet weight), the RDR test was normal in 9 (75 per cent). Inability of the RDR test to predict vitamin A nutriture in patients with protein-energy malnutrition and in patients with liver dysfunction may, in part, be due to inadequate synthesis or release of retinol-binding protein.

Aged↗

1192U90 in animal tests that predict antipsychotic efficacy, anxiolysis, and extrapyramidal side effects.

1192U90 was developed on the assumption that antagonism of 5-HT2 receptors efficacy yields more potently than D2 receptors against positive and negative symptoms of schizophrenia with minimal liability for extrapyramidal side effects (EPSs), and that 5-HT1A agonism further reduces EPSs and provides anxiolytic and antidepressant activity. 1192U90 was submitted to four tests that predict antipsychotic efficacy (antagonism of apomorphine-induced climbing in mouse, antagonism of apomorphine-induced circling in rats with unilateral 6-OHDA lesions, antagonism of amphetamine-induced hyperlocomotion in rat, and inhibition of conditioned avoidance in rat), two tests of 5-HT2 function (antagonism of 5-MeODMT-induced head twitches in mouse and antagonism of 5-HTP-induced wet dog shakes in rat), and three tests that predict EPS liability (antagonism of apomorphine-induced stereotypy in mouse and rat and induction of catalepsy in mouse). ED50s (mg/kg PO) were as follows: climbing 10.1, circling 7.9, hyperlocomotion 6.6, and avoidance 5.7; head twitches 5 and wet dog shakes 4.6; stereotypy in mouse 91.1, stereotypy in rat 133.4, and catalepsy 192.4. The ratio of ED50 for stereotypy antagonism to ED50 for climbing antagonism was 9 (compared to 4, 3, and 4 for clozapine, risperidone, and haloperidol). The ratio of ED50 for catalepsy induction to ED50 for climbing antagonism was 19 (compared to 7, 2, and 17 for clozapine, risperidone, and haloperidol). 1192U90 was also submitted to three tests that predict anxiolysis: It produced only a small increase in punished lever pressing for food in rat (Geller-Seifter conflict test), which is specific for rapid-onset efficacy, but produced large increases in punished key pecking for food in pigeon and cork gnawing in rat, which identify the delayed onset 5-HT1A agonists such as buspirone. The results suggest that 1192U90 would be effective for positive and negative symptoms of schizophrenia, with minimal liability for EPSs, and may also have anxiolytic properties.

Animals↗

Testing to predict outcome after transurethral resection of the prostate.

PURPOSE: We assessed the ability of routine clinical tests to predict outcome following transurethral resection of the prostate. MATERIALS AND METHODS: A total of 556 men randomized into a trial of surgery versus watchful waiting was evaluated preoperatively with symptom interview, quality of life assessment, uroflowmetry, urinalysis, standard chemistry panel, post-void residual urine determination and cystoscopy. The ability to predict avoidance of postoperative complications, and improvement in quality of life and genitourinary symptoms was assessed in the 249 men randomized to undergo transurethral resection of the prostate. RESULTS: Patients with the highest symptom scores were most likely to have symptom improvement and those most bothered by the symptoms were most likely to have improvement in quality of life. No objective tests measuring physiological parameters made clinically significant contributions toward predicting these outcomes. Lower obstructive symptom scores and larger perioperative infusions of intravenous fluids were associated with a greater chance of complications. CONCLUSIONS: Symptom analysis and quality of life assessment are most useful in selecting patients for transurethral resection of the prostate. Objective diagnostic tests are of limited additional benefit.

Follow-Up Studies↗

Predictive genetic testing: high risk expectations in the face of low risk information.

The aims of this cross-sectional, questionnaire study were (1) to estimate the proportion of those receiving negative ("low risk") results following predictive genetic testing who expect to undergo clinically unnecessary future screening and (2) to examine the factors associated with this expectation. Of 127 adults receiving negative results following predictive genetic testing for familial adenomatous polyposis (FAP), 54 people (42%) were expected to attend for future bowel screening. The main predictor was doubt about the accuracy of genetic test results. Expecting to attend was also associated univariately with perceiving the chance of developing FAP as higher, being more worried about this, perceiving the test result to be more uncertain and threatening, and holding a behavioral model of the cause of FAP. Attendance for health screening may be influenced by people's perception of the accuracy of genetic tests that they have undergone. Future research should investigate test presentation and influences on test perception.

Adult↗

The accuracy of the critical velocity test for predicting time to exhaustion during treadmill running.

The purpose of this investigation was to determine the accuracy of the critical velocity (CV) test for predicting time to exhaustion (time limit = TL) during treadmill running. Ten adult males (mean +/- SD of age = 23 +/- 2 years) volunteered to perform a maximal treadmill test, a CV test, and five exhaustive treadmill runs at 70%, 85%, 100%, 115% and 130% of CV for the determination of actual TL. Related t-tests revealed significant (p less than 0.05) differences between the predicted and actual TL values for velocities equal to 100 and 130% of CV. The correlations between predicted and actual TL values for velocities above CV ranged from r = 0.957 to 0.980 (SEE = 0.28-0.82 minutes). At 100% of CV, the subjects maintained the running pace for an average of 16.43 +/- 6.08 minutes (range = 9.96-31.90 minutes) while, at 85% of CV, 8 of the 10 subjects were able to maintain the running pace for 60 minutes. These findings did not support the validity of the CV test for predicting the actual TL during treadmill running and indicated that, in 20% of the cases, CV overestimated the running velocity that could be maintained for 60 minutes by greater than 15%.

Adult↗

Skin testing in predicting response to nasal provocation with alternaria.

OBJECTIVE: Examine the efficacy of epicutaneous and intradermal testing in predicting response to nasal provocation with Alternaria antigen. STUDY DESIGN AND SETTING: Prospective study. Subjects were tested with the Multi-Test II (MT) epicutaneous testing device. Subjects with negative wheals were then tested with a 1:500 weight:volume intradermal injection of Alternaria. They had baseline assessment of nasal cross-sectional area (CSA) using acoustic rhinometry and underwent nasal provocation with increasing Alternaria concentrations. CSA was assessed at each concentration. A nasal allergen provocation score (NAP) of nasal symptoms as well as a nasal visual analogue scale (VAS) were also completed with each concentration. RESULTS: Sensitivity and specificity of MT in predicting nasal response to Alternaria were poor at 42% and 44%, respectively. The addition of intradermal testing increased sensitivity only modestly to 58%. hierarchical linear modeling analysis demonstrated that subjects positive to Alternaria on skin testing did not show a significant reduction in nasal CSA on acoustic rhinometry or significant elevations in two nasal symptom scores with direct nasal provocation. CONCLUSION AND SIGNIFICANCE: Skin testing with either epicutaneous or intradermal testing may not be an accurate or sufficient technique in the assessment of Alternaria reactivity. These results suggest that mold allergies may involve more complex immune mechanisms than simply an immunoglobulin (Ig)E mediated type I immediate hypersensitivity response alone. An alternate model for mold sensitivity, as well as modifications in testing methods, may be required in the evaluation of mold allergy.

Adolescent↗

ETOPE: Evolutionary test of predicted exons.

Since a large number of computationally predicted exons are not supported by existing sequence (e.g. ESTs) or experimental (e.g. expression analysis) data they need to be validated by other methods. ETOPE is designed to test computational predictions by using signals that have not been included in any current computational prediction method. The test is based on the ratio of non-synonymous to synonymous substitution rates between sequences from different genomes. It has been previously shown, by empirical data and computer simulation, to be a powerful criterion for identifying protein-coding regions. The ETOPE is available at http://nekrut.uchicago.edu/etope/.

Amino Acid Substitution↗

Failure of the TRH test to predict the clinical course of patients in remission after antithyroid drug therapy for Graves' disease.

In an attempt to assess the predictive value of the TRH test in patients in remission after stopping antithyroid drugs for thyrotoxicosis, 11 euthyroid patients with a subnormal (group I) and 23 euthyroid patients with a normal serum TSH response to TRH (group II) were followed-up for one year. The mean +/- SE intervals since the withdrawal of drug therapy were 23.2 +/- 1.6 and 20.4 +/- 0.7 months, respectively, at the outset of the study. Five patients (45%) from group I and 7 patients (30%) from group II relapsed during the period of observation. In addition, a change from a subnormal TSH response to TRH and vice versa occurred in some patients. It is not possible to predict by means of the TRH test the subsequent clinical course of patients in remission following antithyroid drug therapy.

Adult↗

Testing phylogeographic predictions on an active volcanic island: Brachyderes rugatus (Coleoptera: Curculionidae) on La Palma (Canary Islands).

Volcanic islands with well-characterized geological histories can provide ideal templates for generating and testing phylogeographic predictions. Many studies have sought to utilize these to investigate patterns of colonization and speciation within groups of closely related species across a number of islands. Here we focus attention within a single volcanic island with a well-characterized geological history to develop and test phylogeographic predictions. We develop phylogeographic predictions within the island of La Palma of the Canary Islands and test these using 69 haplotypes from 570 base pairs of mitochondrial DNA cytochrome oxidase II sequence data for 138 individuals of Brachyderes rugatus rugatus, a local endemic subspecies of curculionid beetle occurring throughout the island in the forests of Pinus canariensis. Although geological data do provide some explanatory power for the phylogeographic patterns found, our network-based analyses reveal a more complicated phylogeographic history than initial predictions generated from data on the geological history of the island. Reciprocal illumination of geological and phylogeographic history is also demonstrated with previous geological speculation gaining phylogeographic corroboration from our analyses.

Animals↗

The effect of mechanical interlocking on crystal packing: predictions and testing.

The first statistical analyses of the X-ray crystal structures of mechanically interlocked molecular architectures, the first molecular mechanics-based solid-state calculations on such structures and atomic force microscopy (AFM) experiments are used in combination to predict and test which types of benzylic amide macrocycle-containing rotaxanes possess mobile components in the crystalline phase and thus could form the basis of solid-state devices that function through mechanical motion at the molecular level. The statistical studies and calculations show that crystals formed by rotaxanes possess similarities and unanticipated differences with respect to the crystal packing of noninterlocked molecules. Trends in the rotaxane series correlate quantities related to crystal packing, molecular size, stoichiometry, and H-bonding. In accordance with the findings of Gavezzotti et al. for conventional molecular architectures, a principal component analysis (PCA) showed that three vectors related to the size, packing parameters, and stoichiometry are sufficient to describe the crystal properties of benzylic amide macrocycle-containing rotaxanes. When hydrogen bond-related quantities are included in a second PCA, they combine with the size and the stoichiometry vectors but not with packing-related parameters, indicating that the intramolecular "saturation" of the H-bonds (between the interlocked components) takes precedence over crystal assembly (i.e., intermolecular packing) in these systems. However, cluster analyses also suggest a major role for the energy of interaction between the macrocycle and its crystal environment. The identification of such a "privileged" interaction is of fundamental importance to the development of rotaxanes with in-crystal mobility of one or more of their interlocked components, a prerequisite for the exploitation of molecular level mechanical motion in the solid state. The set of trends found, together with the calculated energies, was used to propose guidelines for which benzylic amide macrocycle-containing rotaxanes are best suited to become building blocks for systems with mobile submolecular units in the crystalline phase. An experimental test of the predictive power of such guidelines was carried out using AFM on a rotaxane and its thread, identified by the study as a promising candidate for solid-state mobility. Intuitively, the rotaxane should be less mobile in the solid state since it has multiple sets of both hydrogen bond donors and acceptors that can form strong inter- and intramolecular H-bonds. Conversely, the thread has no hydrogen bond donors and cannot form such bonds. The AFM experiments, however, confirm the statistical analysis prediction that the rotaxane is considerably more mobile in the solid than the thread.

Journal Article↗

What should we want to know about our future? A Kantian view on predictive genetic testing.

Recent advances in genomic research have led to the development of new diagnostic tools, including tests which make it possible to predict the future occurrence of monogenetic diseases (e.g. Chorea Huntington) or to determine increased susceptibilities to the future development of more complex diseases (e.g. breast cancer). The use of such tests raises a number of ethical, legal and social issues which are usually discussed in terms of rights. However, in the context of predictive genetic tests a key question arises which lies beyond the concept of rights, namely, What should we want to know about our future? In the following I shall discuss this question against the background of Kant's Doctrine of Virtue. It will be demonstrated that the system of duties of virtue that Kant elaborates in the second part of his Metaphysics of Morals offers a theoretical framework for addressing the question of a proper scope of future knowledge as provided by genetic tests. This approach can serve as a source of moral guidance complementary to a justice perspective. It does, however, not rest on the-rather problematic--claim to be able to define what the "good life" is.

Ethical Theory↗

Strategies for identifying false positive responses in predictive skin sensitization tests.

It is important that predictive toxicological test methods are selective for their intended endpoint and that their limitations are understood and acknowledged. The local lymph node assay (LLNA) is a relatively new predictive test for skin sensitization potential that can replace traditional guinea pig tests and offers significant scientific and animal welfare advantages. However, there has been some concern that certain irritant materials may yield false positive results, although it must be emphasized that false positives also occur in guinea pig methods. Consequently, we have examined the performance in the LLNA of a range of skin irritants, from varying chemical classes and covering a range of irritation potency. The results presented here demonstrate clearly that the majority of skin irritants are negative in the LLNA. These results are reviewed in the context of the occurrence of false positive reactions in the guinea pig maximization test and the strategies for dealing with such results are discussed. The need for careful scientific evaluation of the results in all predictive tests for sensitization is thus emphasized. In terms of specificity, the LLNA has been more fully evaluated than other predictive test methods and is at least as accurate. In terms of animal welfare, objectivity, reproducibility and reliability it is superior to other methods. In summary, all predictive skin sensitization test results should be evaluated in a scientifically rigorous manner and the additional data provided herein further support the adoption of the LLNA as a complete replacement for the traditional guinea pig methods.

Animals↗

Do thyroid function tests independently predict survival in the critically ill?

We studied the ability of thyroid function tests to predict hospital survival in 116 critically ill patients and compared the results with independent predictions of survival made by critical care physicians. Eleven patients (9.5%) had clinically unsuspected hypothyroidism and were less likely to survive (p = 0.03). In patients critically ill with nonthyroidal disease, low T3, low FT3I, low T4, low FT4I, high TSH, and high T3U levels each showed significant correlation with nonsurvival (all p less than 0.02). Of these, however, only low T3 (p less than 0.001) and high TSH (p = 0.016) showed significant independent prediction of nonsurvival, and only low T3 (p = 0.011) added any significant independent prediction of nonsurvival beyond that made clinically by the group of critical care physicians.

Critical Illness↗

Prediction of late failure after medical abortion from serial beta-hCG measurements and ultrasonography.

BACKGROUND: Surgical treatment of failed medical abortion may be performed several weeks after initiation of the abortion. There are no recognized methods for early identification of these late failures. We assessed the prognostic values of beta-hCG and ultrasonography in predicting late failure after medical abortion. METHODS: A total of 694 consecutive women with gestational age (GA) <63 days were followed up with beta-hCG measurements initially on the day of treatment and on day 8 and day 15, after the medically induced abortion with mifepristone and gemeprost. Measurement of the endometrial thickness by ultrasonography was performed on day 15 after induction of medical abortion. Failures diagnosed after day 15 and within 15 weeks were identified and classified as late failures. All interventions in this group were due to bleeding problems. The predictive values of different absolute and relative beta-hCG levels and different endometrial thickness were analysed. RESULTS: Of all failures in the study period, 65% (32) were diagnosed after the 2 week follow-up, and categorized as late failures. The absolute and the relative beta-hCG values on days 8 and 15 as well as the endometrial thickness on day 15 were greater among late failures than successes. Used as a predictive test, the positive predictive values of these variables were low. CONCLUSION: Neither beta-hCG nor endometrial thickness can be used clinically as diagnostic tests in predicting late failure after medical abortion.

Abortifacient Agents, Steroidal↗

A new qualitative interleukin-6 bedside test can predict pneumonia in patients with severe head injury--comparison to the standard Immulite test and a semiquantitative bedside test.

Severe head injury (SHI) leads to systemic immunosuppression, which is processed by central mechanisms and is associated with a high risk of pneumonia. The timely identification of an immunodepressed condition in SHI patients might help prevent infections by changing the intensive care strategy. The aim of this prospective study is to evaluate a new method for identifying immunodepression and predicting pneumonia. We correlated interleukin (IL)-6 levels determined by the standard test (Immulite) and performed by specialized laboratories with those obtained using the new bedside test (PicoScan) with the occurrence of pneumonia in patients with SHI. Thirty-two patients with isolated SHI were investigated. Analyses were performed on serum samples taken 2 to 24 hours after trauma. Pearson correlation coefficient was 0.924 (P<0.001) for IL-6 values determined by PicoScan versus Immulite and Spearman rho was 0.572 for visual interpretation versus Immulite (P=0.01). Immulite and PicoScan have a positive predictive value of 91% and 100%, respectively, and a negative predictive value of 76% and 86%. The present study investigated for the first time the determination of IL-6 concentrations by PicoScan in patients. Our findings show a good correlation with the results of the standard Immulite test and suggest that the PicoScan may be used as a handy tool to predict pneumonia in SHI patients.

Adolescent↗

Maximal 12-lead exercise testing for prediction of severity of coronary artery disease.

Ninety-three patients with chest pain underwent both maximal 12-lead treadmill testing and coronary arteriography to ascertain whether exercise testing might predict multivessel coronary disease. Twenty-eight patients had normal coronary arteries, 20 single vessel disease (greater than 70% reduction in luminal diameter), 18 double and 22 triple vessel disease. Five patients had left main coronary disease. All 45 patients with double, triple or left main disease had positive 12-lead exercise tests whilst only 15/20 (75%) with single vessel disease had positive tests. Sensitivity of the 12-lead electrocardiogram during maximum stress testing was 92%, with 15% false negatives. The predictive value of a positive test was 100% (no false positives) and 85% for a negative test. Significant predictors of severe triple vessel and left main coronary disease were the sum of ST segment depression (xi ST), the number of ECG leads which developed ST segment depression, the stage at which ST depression developed and the ST segment recovery time. There was a significant correlation between the anatomical location of coronary artery stenoses and the area of ischaemia indicated by the exercise electrocardiogram.

Adult↗